Safety, Tolerability, and Efficacy of IL-15 Superagonist (N-803) With and Without Combination Broadly Neutralizing Antibodies to Induce HIV-1 Control During Analytic Treatment Interruption

NCT ID: NCT04340596

Last Updated: 2025-03-25

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

ACTIVE_NOT_RECRUITING

Clinical Phase

PHASE1

Total Enrollment

118 participants

Study Classification

INTERVENTIONAL

Study Start Date

2021-05-21

Study Completion Date

2026-12-30

Brief Summary

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The purpose of this study is to evaluate the safety, tolerability, and efficacy of N-803, an IL-15 superagonist, with or without combination broadly neutralizing antibodies (bNAbs), to induce HIV-1 control during analytic treatment interruption (ATI).

Detailed Description

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This study will evaluate the safety, tolerability, and efficacy of N-803, an IL-15 superagonist, with or without combination broadly neutralizing antibodies (bNAbs), to induce HIV-1 control during analytic treatment interruption (ATI).

Participants will be screened for eligibility and undergo leukapheresis, and a subset will also undergo optional rectal biopsy and/or lymph node fine needle aspirations (FNAs) (Step 1).

After pre-entry and determination of eligibility in Step 1, participants will be randomized before Step 2 entry to either the N-803 only arm (Arm A) or the N-803 with combination bNAbs arm (Arm B):

* Arm A will receive a dose of N-803, 6 mcg/kg, subcutaneously 1 week after Step 2 entry and then every 3 weeks for a total of eight doses (during the first 22 weeks).
* Arm B will receive the following (during the first 22 weeks):

* Combination bNAb at Step 2 entry with VRC07-523LS dosed at 20 mg/kg and 10-1074 dosed at 30 mg/kg, intravenously;
* A dose of N-803, 6 mcg/kg, subcutaneously 1 week after Step 2 entry and then every 3 weeks for a total of eight doses;
* A second dose of 10-1074 at week 9 of Step 2 dosed at 30 mg/kg, intravenously

After completing randomized treatment (Step 2), participants will interrupt antiretroviral therapy (ART) (Step 3) and will be followed closely to monitor for indications for reinitiation of ART (Step 4).

After Step 2 entry, most participants will be followed for approximately 100 weeks across the remaining three study steps (i.e., Steps 2, 3, and 4).

Step 1 will last up to 90 days, Step 2 will last approximately 52 weeks (study intervention), Step 3 will last up to 24 weeks (ATI), and Step 4 will last 24 weeks (ART restart).

Conditions

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HIV Infection

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Arm A: N-803 only

Participants will receive N-803 6 mcg/kg 1 week after Step 2 entry and then every 3 weeks for a total of eight doses.

Group Type EXPERIMENTAL

N-803 (IL-15 Superagonist)

Intervention Type BIOLOGICAL

Administered by subcutaneous (SQ) injection

Arm B: N-803 in combination with 10-1074 and VRC07-523LS

Participants will receive N-803 in combination with 10-1074 and VRC07-523LS as follows:

* At Step 2 entry:

* VRC07-523LS 20 mg/kg
* 10-1074 30 mg/kg
* At Step 2, week 1: N-803 6 mcg/kg every 3 weeks for eight doses
* At Step 2, week 9: 10-1074 30 mg/kg

Group Type EXPERIMENTAL

N-803 (IL-15 Superagonist)

Intervention Type BIOLOGICAL

Administered by subcutaneous (SQ) injection

VRC07-523LS

Intervention Type BIOLOGICAL

Administered by intravenous (IV) infusion

10-1074

Intervention Type BIOLOGICAL

Administered by intravenous (IV) infusion

Interventions

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N-803 (IL-15 Superagonist)

Administered by subcutaneous (SQ) injection

Intervention Type BIOLOGICAL

VRC07-523LS

Administered by intravenous (IV) infusion

Intervention Type BIOLOGICAL

10-1074

Administered by intravenous (IV) infusion

Intervention Type BIOLOGICAL

Eligibility Criteria

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Inclusion Criteria

* HIV-1 infection
* On ART for at least 96 weeks prior to randomization
* On ART regimen containing an integrase inhibitor and two nucleoside reverse transcriptase inhibitors (NRTIs) or dolutegravir/lamivudine for at least 6 weeks prior to randomization.
* CD4 cell count \>450 cells/mm\^3 within 90 days prior to randomization
* CD4 cell count nadir ≥200 cells/mm\^3.
* Plasma HIV-1 RNA levels of \<50 copies/mL for at least 96 weeks prior to randomization
* Select laboratory results within 90 days of randomization
* IC90 to 10-1074 of ≤1.5 mcg/mL, 10-1074 maximum percent inhibition (MPI) ≥98%, and IC80 to VRC07-523LS of ≤1 mcg/mL on the Monogram PhenoSense assay.
* QTcF interval ≤440 msec within 90 days prior to randomization.
* For cisgender women and transgender men of reproductive potential, negative urine or serum pregnancy test within 30 days prior to randomization
* Cisgender women and transgender men of reproductive potential must agree to use two methods of contraception, if participating in sexual activity that could lead to pregnancy.
* Cisgender men and transgender women participants engaging in sexual activity that could lead to pregnancy and who are of reproductive potential must agree to use a barrier method of contraception
* Willingness to abstain from sexual intercourse or use a barrier method of contraception consistently
* Willingness to participate in an ATI.
* Weight \>50 kg and \<115 kg.
* Completion of pre-entry leukapheresis

Exclusion Criteria

* History of AIDS-defining illness, with the exception of recurrent pneumonia.
* History of or current clinical cardiovascular disease
* Current clinically significant acute or chronic medical condition
* History of HIV-associated neurocognitive disease
* History of an HIV-associated malignancy
* ART initiated during acute HIV infection
* Current receipt of ART other than NRTI and integrase inhibitor.
* Resistance to one or more drugs in two or more ARV drug classes.
* Receipt of any therapeutic HIV vaccine or monoclonal antibody therapy (anti-HIV or otherwise) at any time in the past.
* History of prior immunoglobulin (IgG) therapy.
* History of use of any immunomodulatory medications within 6 months prior to randomization
* Participation in another clinical study of an investigational product currently or within past 12 weeks
* Breastfeeding or pregnancy
Minimum Eligible Age

18 Years

Maximum Eligible Age

65 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Rockefeller University

OTHER

Sponsor Role collaborator

ImmunityBio, Inc.

INDUSTRY

Sponsor Role collaborator

National Institute of Allergy and Infectious Diseases (NIAID)

NIH

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Timothy Wilkin, MD, MPH

Role: STUDY_CHAIR

Weill Medical College of Cornell University

Locations

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Alabama CRS (Site ID# 31788)

Birmingham, Alabama, United States

Site Status

UCLA CARE Center CRS

Los Angeles, California, United States

Site Status

UCSD Antiviral Research Center CRS (Site ID: 701)

San Diego, California, United States

Site Status

University of California, San Fransisco HIV/AIDS CRS

San Francisco, California, United States

Site Status

Whitman-Walker Institute, Inc. CRS (Site ID: 31791)

Washington D.C., District of Columbia, United States

Site Status

Northwestern University CRS

Chicago, Illinois, United States

Site Status

Massachusetts General Hospital CRS (MGH CRS) (Site ID: 101)

Boston, Massachusetts, United States

Site Status

Washington University Therapeutics (WT) CRS

St Louis, Missouri, United States

Site Status

New Jersey Medical School Clinical Research Center CRS [Site ID: 31786]

Newark, New Jersey, United States

Site Status

Columbia P&S CRS

New York, New York, United States

Site Status

Weill Cornell Uptown CRS (Site ID: 7803)

New York, New York, United States

Site Status

Chapel Hill CRS (Site ID: 3201)

Chapel Hill, North Carolina, United States

Site Status

Case Clinical Research Site

Cleveland, Ohio, United States

Site Status

Penn Therapeutics, CRS (Site ID: 6201)

Philadelphia, Pennsylvania, United States

Site Status

Countries

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United States

Related Links

Other Identifiers

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38639

Identifier Type: REGISTRY

Identifier Source: secondary_id

ACTG A5386

Identifier Type: -

Identifier Source: org_study_id

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